The goal of this proposal is define the role of vascularization in metastasis and to identify the role of pathophysiological insults in the metastatic process. The investigations will be performed using magnetic resonance imaging (MRI) and spectroscopy (MRS) to examine orthotopic and subcutaneous human prostate cancer models in SCID mice and isolated human prostate cancer cells. The proposed studies are designed to test the hypotheses that: (1) cell lines preselected for higher invasive and metastatic potential will induce and exhibit a higher vascular volume or permeability or both; and (2) a significant fraction of the histologically identified vessels are not functional and the resultant hostile environment (low pH, oxygen, and glucose) increases the invasive behavior of a sub-population of cells.
The aims of the in vivo studies are: (a) to characterize vasculature in terms of vascular volume and permeability using high resolution MRI for comparison with immunohistochemical measurements of Factor VIII and vascular endothelial growth factor (VEGF) expression; and (b) increase either the tumor vascularization by mixing the injection inoculum with dextran beads loaded with basis fibroblast growth factor (bFGF) or both tumor vascularization and permeability by mixing the inoculum with dextran beads loaded with VEGF.
The aim of the cell studies is to develop a """"""""Metabolic Boyden Chamber"""""""" for MR studies of metabolism and invasion of isolated and perfused cells to determine the role of the lactate concentration, pH and oxygen tension in invasion.
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